EP0995749A1 - Reinigungs- und Kristallisationsverfahren für Riboflavin - Google Patents
Reinigungs- und Kristallisationsverfahren für Riboflavin Download PDFInfo
- Publication number
- EP0995749A1 EP0995749A1 EP99120364A EP99120364A EP0995749A1 EP 0995749 A1 EP0995749 A1 EP 0995749A1 EP 99120364 A EP99120364 A EP 99120364A EP 99120364 A EP99120364 A EP 99120364A EP 0995749 A1 EP0995749 A1 EP 0995749A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- riboflavin
- activated carbon
- crystallization
- temperature
- solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B63/00—Purification; Separation; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D475/00—Heterocyclic compounds containing pteridine ring systems
- C07D475/12—Heterocyclic compounds containing pteridine ring systems containing pteridine ring systems condensed with carbocyclic rings or ring systems
- C07D475/14—Benz [g] pteridines, e.g. riboflavin
Definitions
- the present invention relates to a new method for cleaning and Crystallization of riboflavin for pharmaceutical and food applications.
- Riboflavin is usually dissolved in an acidic or alkaline environment. Cell remnants, Proteins, peptides and amino acids that are released after the riboflavin itself is dissolved Depending on the substance, they can be dissolved or undissolved relatively large effort by combining several different Unit operations separable.
- the dissolved riboflavin is usually through different processes mostly crystallized above 30 ° C, as acicular crystals, which normally the stable modification A (See, for example, U.S.
- Patents 2,324,800, 2,797,215 and 4,687,847) Furthermore, riboflavin has so far been used exclusively in the stable Crystal modification A manufactured and sold. Because riboflavin in this form only to a very small extent is water-soluble, that is for pharmaceutical and food applications necessary loosening behavior relatively bad. For quite some time there is therefore a desire to dissolve and thus also bioavailability of riboflavin to improve.
- the riboflavin currently marketed is partly in the form of very fine powder, sometimes in the form of long yellow needles.
- the fine powder dusted considerably has a very low bulk density and poor flow behavior and charges very easily, for example pressing into tablets is difficult and additives for improvement flow and compacting behavior are required.
- the needles also show a lot of dust during processing and are problematic in Further processing, such as in the case of flour vitaminization.
- various agglomeration processes that took place during the crystallization So far not used for the industrial production of riboflavin see for example, Canadian Patent 633,852 and European Patent 307,767). Further agglomeration processes take place at the Drying using acicular crystals of modification A (German Offenlegungsschrift 4,014,262).
- the aim of the present invention is based on needle-shaped Riboflavin, which corresponds to the stable modification A and synthetic or has been produced biotechnologically, a purer riboflavin with over 98% To produce content of riboflavin, which significantly better dissolving and Has flow properties than the currently available material. in the in general, the new riboflavin should have better bioavailability and better physical properties, e.g. when tableting.
- the method according to the invention is a method for the purification and crystallization of riboflavin, which is characterized in that needle-shaped riboflavin of the stable modification A in an aqueous Mineral acid solution at a temperature not exceeding about 30 ° C.
- the medium containing the activated carbon is a cross-flow filtration over a Ceramic membrane with a pore size of about 20 to about 200 nm, the resulting filtrate with a five to ten times (v / v) water at a temperature not exceeding about 30 ° C, and the resulting precipitated, spherical crystals of riboflavin Centrifugation or filtration separates.
- the crystals After receiving the riboflavin crystals in this way, the crystals can optionally washed with water and then after itself known methods can be dried.
- the procedure supplemented in this way represents one represents another aspect of the inventive method defined above.
- acicular riboflavin of modification A used such as in of production for animal feed.
- This riboflavin usually has one Content from about 85 to about 98% and chemical depending on the production method By-products and / or fermentation residues and water on whose The total amount is accordingly over 2 percent by weight.
- the raw material becomes dry or fitter-moist dissolved in the aqueous mineral acid solution. This is followed by the resolution a protonation reaction.
- fermentation residues such as Proteins, peptides and amino acids, and / or chemical by-products free that then partially dissolved and partially present as a solid.
- the concentration is expediently in the range from about 18 to about 24%.
- one aqueous hydrochloric acid solution up to about 19% dry riboflavin are dissolved. The solution is almost saturated.
- the amount depends Riboflavin versus the amount of aqueous mineral acid according to the nature of the Mineral acid, the concentration of the solution and the dissolution temperature.
- the acicular riboflavin is dissolved in the aqueous Mineral acid solution at temperatures up to a maximum of 30 ° C, usually at about 5 to about 25 ° C, preferably at about 10 to about 20 ° C, conveniently with intensive mixing, for example by intensive Stir.
- the Release time can be reduced. Depending on the temperature and degree of mixing lasts the complete dissolution process usually takes up to about 30 minutes.
- activated carbon is added to the solution of the riboflavin in the aqueous mineral acid solution.
- the dissolved impurities are adsorbed on the activated carbon.
- This can be powdered or granulated.
- about 0.5 to about 9% (weight percent), preferably about 3%, activated carbon, based on the riboflavin content, is added for the adsorptive purification of the dissolved impurities from the solution.
- the activated carbon is left in the solution for up to about 12 hours, preferably about 0.5 to about 3 hours.
- Suitable as activated carbon is acid-washed activated carbon with a bulk density of about 250 to about 400 kg / m 3 , preferably about 300 kg / m 3 , a specific surface area of about 1200 to about 1600 m 2 / g, preferably about 1400 m 2 / g , and an average particle size of about 20 to about 70 microns.
- suitable activated carbons are Norit® CA1 and Bentonorit® CA1, which are particularly suitable for the adsorption of dissolved biological contaminants, and Norit® SX2, which in turn is particularly suitable for the separation of chemical contaminants.
- aqueous mineral acid solution in addition to activated carbon a filter aid can be added, of which approximately 2 to about 9 percent by weight based on the riboflavin content.
- Filter aids are, for example, Arbocel® BWW 40 and B 800 from the company Rettenmaier & Sons GmbH + Co.
- the separation of the activated carbon and any filter aid that may be present and the undissolved fermentation residues are carried out using the subsequent cross-flow filtration. It was surprisingly found that the activated carbon has an abrasive effect on the Surface layer shows that forms on the membrane. Because of this effect it is only possible, the membrane stable over a longer period with almost the operate twice the throughput than without activated carbon.
- the activated carbon come So both abrasive and adsorptive properties.
- Cross flow filtration takes place over a ceramic membrane, which has a pore size of about 20 to about 200 nm, preferably about 50 nm.
- the in circulation pumped activated carbon causes the abrasion to clean itself the top layer of coal and fermentation residues that build up the membrane.
- the Cross-flow velocity across the membrane is usually relatively high; she is expediently in the range from about 5 to about 6 m / s.
- To the The transmembrane is not to compress the top layer excessively Pressure suitably 1 to 2 bar (0.1 to 0.2 MPa).
- the temperature of the medium in which the crystallization takes place can vary according to the production method and degree of contamination of the riboflavin in one Range can be varied from 0 to 30 ° C. Especially with synthetic manufactured material, the temperature can be increased up to 30 ° C; at fermentative or relatively clean material are generally available Temperatures below 10 ° C. However, a temperature is preferred set between 4 and 10 ° C.
- the crystallization can be carried out batchwise or be carried out continuously, preferably continuously. As a crystallizer cascades or individual boilers can be used. Especially at individual boilers, it is recommended at different points in the boiler feed. In any case, inside the crystallizer must be a very good one Macroscopic mixing can be set.
- the Feed solutions offset by 180 ° on the upper and lower stirrer levels be fed. This is conveniently done on the upper level Water, on the lower the mineral acid solution of riboflavin added.
- the Stirring should be very gentle, so as not to clog the crystals to destroy.
- the residence time is suitably about 5 to about 20 minutes, preferably about 10 to 13 minutes.
- the subsequent filtration is carried out with a filter or a centrifuge; a band filter is preferably used, on which the laundry that may be carried out is also very efficient.
- the Drying can be carried out in a manner known per se.
- the initial relative supersaturation in the crystallizer can by returning the mother liquor from the laundry with the Crystalline incoming water can be adjusted.
- Mother liquor: water is conveniently about 1: 1 to about 1: 8.
- the Relative supersaturation can occur via the conductivity in the crystal are judged, ideally a range from about 170 to about 200 mS / cm is observed.
- the return of the Mother liquor can be dispensed with. In the case of repatriation, it is preferred governed by the conductivity established in the crystallizer.
- the crystals are filtered or centrifuged severed.
- the filter cake is then preferably washed with water, after which the moist filter cake can be dried.
- Riboflavin produced by fermentation was used as the starting material for the process described below, which had a riboflavin content of 97.02% (according to HPLC), a residual moisture content (H 2 O) of 0.80% and an amino acid content of 1.11% and was present as needle-shaped crystals of the stable modification A.
- 350.0 g of this starting material were in 1708.6 g of 24% hydrochloric acid dissolved at 22 ° C with stirring. After a release time of about 15-20 minutes there was a brown-black solution that contained about 17% riboflavin.
- the 3 l precipitation crystal was first filled with about 2 l water and the Liquid stirred with a two-stage inclined blade stirrer at 100 rpm and then cooled to 10 ° C. Thereafter it became 1590 continuously g / h hydrochloric riboflavin solution on the top stirrer and about 9000 g / h water metered into the lower stirrer at about 10 ° C. About 2 - 4 minutes after the Start began to crystallize the riboflavin as orange-yellow crystals. To At the beginning, the precipitated crystals looked like flakes, but after 20-30 Minutes passed into granular particles. The crystal suspension was then continuously drained after the 3 l mark (double jacket end) had been reached (i.e. after about 7 minutes). The valve became like this set that the level settled at the 3 l mark. The draining Suspension was placed directly on a P3 filter and the solid from there separated from the solution.
- Example 2 As described in Example 1, a riboflavin solution was prepared and activated carbon was added. In contrast to Example 1, the solution was cleaned over a membrane with a pore size of about 50 nm. The transmembrane pressure was 1.5 to 1.7 bar (0.15 to 0.17 MPa), the cross-flow speed 5 to 6 m / s. The permeate throughput was about 70 l / m 2 / h. The crystallization, filtration and washing were carried out analogously to Example 1. The crystallization temperature was between 9 and 10 ° C., and the drying was carried out in a laboratory drying cabinet at 100 ° C.
- Example 2 Chemically produced riboflavin with a Content of 98% used.
- the starting material was as in Example 1 described, solved.
- the crossflow filtration was carried out as described in Example 2.
- the crystallization was carried out at 20 ° C. and in the 1030 g / h hydrochloric acid riboflavin solution and 15060 g / h of water were metered in. Filtration and washing were carried out analogously to Example 1. Drying was carried out analogously to Example 2 carried out.
- the missing percentage includes the water content and others low contamination.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicinal Preparation (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Description
Reinheiten und Eigenschaften des jeweils getrockneten Endproduktes | |||||
Beispiel | Modifikation (nach Röntgen-Strukturanalyse) | Riboflavin-Gehalt (nach HPLC) | Lumichrom-Gehalt (nach HPLC) | Lumiflavin-Gehalt (nach HPLC) | AminosäureGehalt |
1 | B | 98% | 0,08% | - | 0,1% |
2 | B | 98,9% | 0,15% | - | 0,06% |
3 | B | 99% | 0,15% | 0,25% | - |
Claims (11)
- Verfahren zur Reinigung und Kristallisation von Riboflavin , dadurch gekennzeichnet, dass man nadelförmiges Riboflavin der stabilen Modifikation A in einer wässrigen Mineralsäurelösung bei einer etwa 30°C nicht übersteigenden Temperatur unter intensiver Durchmischung auflöst, zur resultierenden Lösung Aktivkohle zugibt, nach Adsorption der gelösten Verunreinigungen aus der Lösung auf der Aktivkohle das die Aktivkohle enthaltende Medium einer Querstromfiltration über eine Keramikmembran mit einer Porengrösse von etwa 20 bis etwa 200 nm unterwirft, das resultierende Filtrat mit einer fünf- bis zehnfachen Menge (Vol. /Vol.) Wasser bei einer etwa 30°C nicht übersteigenden Temperatur versetzt, und die resultierenden ausgefallenen, sphärischen Kristalle von Riboflavin durch Zentrifugation oder Filtration abtrennt.
- Verfahren nach Anspruch 1, dadurch gekennzeichnet, dass die so erhaltenen sphärischen Kristalle von Riboflavin mit Wasser gewaschen und anschliessend getrocknet werden.
- Verfahren nach Anspruch 1 oder 2, dadurch gekennzeichnet, dass die Mineralsäure Salzsäure oder Salpetersäure, vorzugsweise Salzsäure, ist.
- Verfahren nach einem der Ansprüche 1 bis 3, dadurch gekennzeichnet, dass die Auflösung des nadelförmigen Riboflavins in der wässrigen Mineralsäurelösung bei etwa 5 bis etwa 25°C, vorzugsweise bei etwa 10 bis etwa 20°C, erfolgt.
- Verfahren nach einem der Ansprüche 1 bis 4, dadurch gekennzeichnet, dass zur Lösung des nadelförmigen Riboflavins in der wässrigen Mineralsäurelösung etwa 0,5 bis etwa 9% (Gewichtsprozent),vorzugsweise etwa 3%, Aktivkohle bezogen auf den Riboflavingehalt zugegeben werden.
- Verfahren nach einem der Ansprüche 1 bis 5, dadurch gekennzeichnet, dass als Aktivkohle sauer gewaschene Aktivkohle mit einer Schüttdichte von etwa 250 bis etwa 400 kg/m3, vorzugsweise etwa 300 kg/m3, einer spezifischen Oberfläche von etwa 1200 bis etwa 1600 m2/g, vorzugsweise etwa 1400 m2/g, und einer mittleren Partikelgrösse von etwa 20 bis etwa 70 µm verwendet wird.
- Verfahren nach einem der Ansprüche 1 bis 6, dadurch gekennzeichnet, dass neben Aktivkohle ein Filterhilfsmittel zugegeben wird.
- Verfahren nach einem der Ansprüche 1 bis 7, dadurch gekennzeichnet, dass die Keramikmembran eine Porengrösse von etwa 50 nm aufweist.
- Verfahren nach einem der Ansprüche 1 bis 8, dadurch gekennzeichnet, dass die Temperatur des Mediums, in dem die Kristallisation stattfindet, in einem Bereich von etwa 4 bis etwa 10°C liegt.
- Verfahren nach einem der Ansprüche 1 bis 9, dadurch gekennzeichnet, dass das Verfahren kontinuierlich durchgeführt wird, und die Verweilzeit im Kristaller bei der Kristallisation etwa 5 bis etwa 25 Minuten, vorzugsweise etwa 10 bis 13 Minuten, beträgt.
- Verfahren nach einem der Ansprüche 1 bis 10, dadurch gekennzeichnet, dass die resultierenden ausgefallenen, sphärischen Kristalle von Riboflavin auf einem Bandfilter gesammelt, abgetrennt und getrocknet werden.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP99120364A EP0995749B1 (de) | 1998-10-19 | 1999-10-13 | Reinigungs- und Kristallisationsverfahren für Riboflavin |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP98119686 | 1998-10-19 | ||
EP98119686 | 1998-10-19 | ||
EP99120364A EP0995749B1 (de) | 1998-10-19 | 1999-10-13 | Reinigungs- und Kristallisationsverfahren für Riboflavin |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0995749A1 true EP0995749A1 (de) | 2000-04-26 |
EP0995749B1 EP0995749B1 (de) | 2007-03-07 |
Family
ID=8232818
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP99120364A Expired - Lifetime EP0995749B1 (de) | 1998-10-19 | 1999-10-13 | Reinigungs- und Kristallisationsverfahren für Riboflavin |
Country Status (10)
Country | Link |
---|---|
US (1) | US6150364A (de) |
EP (1) | EP0995749B1 (de) |
JP (1) | JP4560155B2 (de) |
KR (1) | KR100647951B1 (de) |
CN (1) | CN1117752C (de) |
AT (1) | ATE356125T1 (de) |
BR (1) | BR9905331A (de) |
CA (1) | CA2282908A1 (de) |
DE (1) | DE59914237D1 (de) |
ES (1) | ES2283090T3 (de) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1048668A2 (de) * | 1999-04-30 | 2000-11-02 | F. Hoffmann-La Roche Ag | Verfahren zur Herstellung von Riboflavinsprühgranulaten |
WO2004089889A2 (de) * | 2003-04-11 | 2004-10-21 | Basf Aktiengesellschaft | Verfahren zur herstellung von riboflavin der modifikation b/c in granulatform |
US7670800B2 (en) | 2003-07-22 | 2010-03-02 | Dsm Ip Assets B.V. | Process for the purification of riboflavin |
CN102809658A (zh) * | 2012-09-03 | 2012-12-05 | 南开大学 | 一种维生素b2的酶联免疫检测试剂盒 |
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CN1765897B (zh) * | 2004-10-27 | 2010-06-23 | 上海凯赛生物技术研发中心有限公司 | 核黄素发酵液的提取工艺 |
TW200826957A (en) * | 2006-10-16 | 2008-07-01 | Teva Gyogyszergyar Zartkoruen Mukodo Reszvenytarsasag | Purification processes for echinocandin-type compounds |
CN104473269A (zh) * | 2014-11-21 | 2015-04-01 | 安徽农业大学 | 一种提高水性溶液中核黄素光稳定性的方法及其应用 |
CN109851619B (zh) * | 2019-02-02 | 2021-04-23 | 赤峰制药股份有限公司 | 一种核黄素提纯工艺 |
CN110272424A (zh) * | 2019-06-29 | 2019-09-24 | 赤峰制药股份有限公司 | 一种从核黄素发酵液中提取核黄素的方法 |
CN111595961B (zh) * | 2020-04-30 | 2021-06-25 | 南京海纳医药科技股份有限公司 | 一种维生素b2有关物质的检测方法 |
CN112022832A (zh) * | 2020-09-24 | 2020-12-04 | 玉溪健坤生物药业有限公司 | 一种nad呼吸链高品质配方原料及制备软胶囊内容物的方法 |
CN113383748A (zh) * | 2021-07-16 | 2021-09-14 | 利津和顺北京鸭养殖有限公司 | 一种可提高肉鸭孵化率的肉鸭孵化方法 |
CN113943291B (zh) * | 2021-11-30 | 2023-09-08 | 湖北广济药业股份有限公司 | 一种核酸酶去除核黄素中的残留dna的方法 |
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US2324800A (en) * | 1941-08-14 | 1943-07-20 | Pfizer Charles & Co | Purification of riboflavin |
US2603633A (en) * | 1950-01-26 | 1952-07-15 | Commercial Solvents Corp | Crystalline form of riboflavin |
US2797215A (en) * | 1955-04-28 | 1957-06-25 | Commercial Solvents Corp | Production of type a riboflavin crystals |
EP0164704A2 (de) * | 1984-06-12 | 1985-12-18 | BASF Aktiengesellschaft | Verfahren zur Reinigung von Riboflavin |
EP0307767A1 (de) * | 1987-09-18 | 1989-03-22 | F. Hoffmann-La Roche Ag | Neue Form des Riboflavins |
JPH01254222A (ja) * | 1988-03-31 | 1989-10-11 | Kubota Ltd | 膜分離処理方法 |
DE4014262A1 (de) * | 1990-05-04 | 1991-11-07 | Basf Ag | Gut rieselfaehige, nichtstaubende bindemittelfreie riboflavinspruehgranulate oder -mikrogranulate aus reinem riboflavin und ein verfahren zu deren herstellung |
EP0464582A2 (de) * | 1990-07-04 | 1992-01-08 | BASF Aktiengesellschaft | Verfahren zur Reinigung von fermentativ hergestelltem Riboflavin |
EP0730034A1 (de) * | 1995-03-03 | 1996-09-04 | F. Hoffmann-La Roche Ag | Reinigung von Riboflavin |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
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CA633852A (en) * | 1962-01-02 | Merck And Co. | Preparation of a free-flowing form of riboflavin | |
JPH07102290B2 (ja) * | 1987-02-18 | 1995-11-08 | 三井研削砥石株式会社 | 濾過方法 |
CN1056845C (zh) * | 1995-03-03 | 2000-09-27 | 弗·哈夫曼-拉罗切有限公司 | 核黄素的纯化 |
-
1999
- 1999-09-20 CA CA002282908A patent/CA2282908A1/en not_active Abandoned
- 1999-10-12 CN CN99121368A patent/CN1117752C/zh not_active Expired - Lifetime
- 1999-10-13 ES ES99120364T patent/ES2283090T3/es not_active Expired - Lifetime
- 1999-10-13 DE DE59914237T patent/DE59914237D1/de not_active Expired - Lifetime
- 1999-10-13 EP EP99120364A patent/EP0995749B1/de not_active Expired - Lifetime
- 1999-10-13 AT AT99120364T patent/ATE356125T1/de not_active IP Right Cessation
- 1999-10-15 JP JP29306399A patent/JP4560155B2/ja not_active Expired - Lifetime
- 1999-10-16 KR KR1019990044908A patent/KR100647951B1/ko active IP Right Grant
- 1999-10-18 BR BR9905331-4A patent/BR9905331A/pt not_active Application Discontinuation
- 1999-10-19 US US09/420,824 patent/US6150364A/en not_active Expired - Lifetime
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US2324800A (en) * | 1941-08-14 | 1943-07-20 | Pfizer Charles & Co | Purification of riboflavin |
US2603633A (en) * | 1950-01-26 | 1952-07-15 | Commercial Solvents Corp | Crystalline form of riboflavin |
US2797215A (en) * | 1955-04-28 | 1957-06-25 | Commercial Solvents Corp | Production of type a riboflavin crystals |
EP0164704A2 (de) * | 1984-06-12 | 1985-12-18 | BASF Aktiengesellschaft | Verfahren zur Reinigung von Riboflavin |
US4687847A (en) * | 1984-06-12 | 1987-08-18 | Basf Aktiengesellschaft | Purification of riboflavin |
EP0307767A1 (de) * | 1987-09-18 | 1989-03-22 | F. Hoffmann-La Roche Ag | Neue Form des Riboflavins |
JPH01254222A (ja) * | 1988-03-31 | 1989-10-11 | Kubota Ltd | 膜分離処理方法 |
DE4014262A1 (de) * | 1990-05-04 | 1991-11-07 | Basf Ag | Gut rieselfaehige, nichtstaubende bindemittelfreie riboflavinspruehgranulate oder -mikrogranulate aus reinem riboflavin und ein verfahren zu deren herstellung |
EP0464582A2 (de) * | 1990-07-04 | 1992-01-08 | BASF Aktiengesellschaft | Verfahren zur Reinigung von fermentativ hergestelltem Riboflavin |
EP0730034A1 (de) * | 1995-03-03 | 1996-09-04 | F. Hoffmann-La Roche Ag | Reinigung von Riboflavin |
Non-Patent Citations (2)
Title |
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CHEMICAL ABSTRACTS, vol. 113, no. 2, 9 July 1990, Columbus, Ohio, US; abstract no. 8823t, page 141; XP002125630 * |
PATENT ABSTRACTS OF JAPAN vol. 14, no. 7 (C - 673) 10 January 1990 (1990-01-10) * |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1048668A2 (de) * | 1999-04-30 | 2000-11-02 | F. Hoffmann-La Roche Ag | Verfahren zur Herstellung von Riboflavinsprühgranulaten |
EP1048668B1 (de) * | 1999-04-30 | 2003-01-29 | F. Hoffmann-La Roche Ag | Verfahren zur Herstellung von Riboflavinsprühgranulaten |
US6723346B1 (en) | 1999-04-30 | 2004-04-20 | Roche Vitamins Inc. | Process for preparing spray granules containing riboflavin |
WO2004089889A2 (de) * | 2003-04-11 | 2004-10-21 | Basf Aktiengesellschaft | Verfahren zur herstellung von riboflavin der modifikation b/c in granulatform |
WO2004089889A3 (de) * | 2003-04-11 | 2005-06-02 | Basf Ag | Verfahren zur herstellung von riboflavin der modifikation b/c in granulatform |
CN100334087C (zh) * | 2003-04-11 | 2007-08-29 | 巴斯福股份公司 | 以颗粒形式制备b/c型的核黄素的方法 |
US7329748B2 (en) | 2003-04-11 | 2008-02-12 | Basf Aktiengesellschaft | Method for the production of riboflavin of modification b/c in granular form |
US7670800B2 (en) | 2003-07-22 | 2010-03-02 | Dsm Ip Assets B.V. | Process for the purification of riboflavin |
CN102809658A (zh) * | 2012-09-03 | 2012-12-05 | 南开大学 | 一种维生素b2的酶联免疫检测试剂盒 |
Also Published As
Publication number | Publication date |
---|---|
EP0995749B1 (de) | 2007-03-07 |
US6150364A (en) | 2000-11-21 |
ATE356125T1 (de) | 2007-03-15 |
BR9905331A (pt) | 2000-08-15 |
KR20000029132A (ko) | 2000-05-25 |
JP4560155B2 (ja) | 2010-10-13 |
JP2000128880A (ja) | 2000-05-09 |
CN1117752C (zh) | 2003-08-13 |
ES2283090T3 (es) | 2007-10-16 |
CA2282908A1 (en) | 2000-04-19 |
KR100647951B1 (ko) | 2006-11-17 |
CN1251365A (zh) | 2000-04-26 |
DE59914237D1 (de) | 2007-04-19 |
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